# Clinical Cases: Nuclear Medicine

## Case 1: Thyroid Cancer Radioiodine Therapy

### Patient Presentation
**Demographics:** 34-year-old female elementary school teacher

**Chief Complaint:** "I had thyroid cancer surgery last month and my surgeon says I need radioactive iodine treatment."

**History of Present Illness:**
A 34-year-old female presents to the nuclear medicine department for radioiodine (I-131) therapy following total thyroidectomy performed 5 weeks ago. She was initially found to have a 2.3 cm thyroid nodule on ultrasound after her primary care physician palpated a firm, non-tender nodule in the right thyroid lobe during a routine exam. Fine needle aspiration biopsy revealed papillary thyroid carcinoma (Bethesda VI). She underwent total thyroidectomy with central neck dissection.

Surgical pathology revealed a 2.5 cm papillary thyroid carcinoma (classical variant) in the right lobe with extrathyroidal extension into the perithyroidal soft tissue and metastatic disease in 2 of 6 central compartment lymph nodes (largest metastatic deposit 0.8 cm). Margins were negative. BRAF V600E mutation was positive on molecular testing. The tumor was staged as pT3aN1a (AJCC 8th edition), Stage I (age <55). ATA risk stratification: intermediate risk.

She has been maintained on levothyroxine since surgery but was switched to liothyronine (T3) 3 weeks ago and then taken off all thyroid hormone replacement 2 weeks ago in preparation for radioiodine therapy. She has been following a low-iodine diet for 2 weeks. She reports symptoms of hypothyroidism including fatigue, constipation, cold intolerance, and weight gain of 3 kg.

**Past Medical History:**
- Papillary thyroid carcinoma (recently diagnosed)
- Total thyroidectomy with central neck dissection (5 weeks ago)
- No other significant medical history

**Medications:**
- All thyroid hormone replacement discontinued 2 weeks ago
- Calcium carbonate 500 mg TID (post-thyroidectomy hypoparathyroidism prophylaxis)
- Calcitriol 0.25 mcg BID

**Social History:**
- Elementary school teacher
- Non-smoker, no alcohol
- Married, no children (desires future pregnancy)
- No radiation exposure history

**Family History:**
- Mother: hypothyroidism (Hashimoto's)
- No family history of thyroid cancer or MEN syndromes

### Physical Examination
- **Vital Signs:** BP 108/68 mmHg, HR 56 bpm, RR 14/min, Temp 36.2°C, SpO2 99% on room air, Weight 68 kg
- **General:** Fatigued-appearing female, periorbital puffiness, dry skin
- **Neck:** Well-healed thyroidectomy scar, no palpable masses or lymphadenopathy in lateral neck compartments
- **Cardiovascular:** Bradycardic, regular rhythm, no murmurs
- **Extremities:** Non-pitting edema of hands and feet, delayed relaxation phase of ankle reflexes
- **Neurological:** Sluggish deep tendon reflexes bilaterally

### Workup and Results

**Laboratory Studies (Pre-RAI therapy):**
| Test | Result | Reference Range |
|------|--------|-----------------|
| TSH | 87 mIU/L | 0.4-4.0 mIU/L (>30 needed for RAI) |
| Thyroglobulin (stimulated) | 12.4 ng/mL | <1 ng/mL (post-thyroidectomy) |
| Anti-thyroglobulin antibodies | <1 IU/mL | <4 IU/mL |
| Free T4 | 0.2 ng/dL | 0.8-1.8 ng/dL |
| Calcium | 8.6 mg/dL | 8.5-10.5 mg/dL |
| Intact PTH | 18 pg/mL | 15-65 pg/mL |
| CBC | Normal | - |
| BMP | Normal | - |
| Urine pregnancy test | Negative | Negative (required pre-RAI) |

**Imaging/Additional Studies:**
- **Pre-therapy diagnostic I-123 whole body scan:** Uptake in thyroid bed (residual thyroid tissue); no distant metastatic uptake identified
- **Neck ultrasound (post-operative):** Small residual tissue in thyroid bed; no suspicious lateral neck lymph nodes
- **RAI Therapy:** 150 mCi (5.55 GBq) I-131 administered orally
- **Post-therapy I-131 whole body scan (7 days post-treatment):** Intense uptake in thyroid bed; faint uptake in two foci in right central neck (consistent with known nodal metastatic disease); no distant metastases; normal physiologic uptake in salivary glands, GI tract, and bladder

### Clinical Image

![Radioiodine Therapy Mechanism](case_01_image.jpg)

*Diagram illustrating the mechanism of radioiodine (I-131) therapy for thyroid cancer: iodine uptake via the sodium-iodide symporter (NIS), intracellular concentration, and beta-particle emission causing targeted DNA damage and cell death in thyroid tissue. Source: Educational illustration.*

### Diagnosis
**Papillary Thyroid Carcinoma, pT3aN1a, Stage I, ATA Intermediate Risk, Status Post Total Thyroidectomy, Treated with I-131 Radioiodine Ablation**

**Key Diagnostic Criteria:**
- Papillary thyroid carcinoma confirmed on surgical pathology with extrathyroidal extension
- Central compartment lymph node metastases (2/6 nodes positive)
- BRAF V600E positive (associated with more aggressive behavior)
- ATA intermediate risk stratification warranting RAI therapy
- Stimulated TSH >30 mIU/L confirming adequate preparation
- Elevated stimulated thyroglobulin (12.4 ng/mL) suggesting residual disease
- Post-therapy scan confirming uptake in thyroid bed and central neck nodes

### Treatment Plan
1. **I-131 dose administered:** 150 mCi (5.55 GBq) -- appropriate for intermediate-risk disease with nodal metastases
2. **Radiation safety precautions:** Patient remains in isolation for 2-3 days; maintain 6-foot distance from others; separate bathroom; no close contact with children or pregnant women for 5-7 days; radiation safety officer to perform survey before discharge
3. **Salivary gland protection:** Sour candy/lemon drops starting 24 hours after RAI to promote salivary flow and reduce sialadenitis risk
4. **Restart thyroid hormone:** Begin levothyroxine 2 mcg/kg/day (137 mcg daily) on day 2 post-RAI; target TSH suppression to 0.1-0.5 mIU/L for intermediate-risk disease
5. **Follow-up:** Stimulated thyroglobulin and diagnostic whole body scan at 6-12 months to assess response; neck ultrasound every 6 months for first 2 years
6. **Fertility counseling:** Recommend delaying pregnancy for 6-12 months post-RAI; reassurance that RAI at this dose does not significantly impair fertility
7. **Long-term monitoring:** Annual thyroglobulin on suppressive levothyroxine; adjust TSH suppression target based on response to therapy

### Key Learning Points
- Radioiodine (I-131) therapy exploits the sodium-iodide symporter (NIS) to selectively deliver targeted radiation to thyroid tissue and differentiated thyroid cancer cells
- Adequate TSH stimulation (>30 mIU/L) is essential for optimal RAI uptake; this can be achieved by thyroid hormone withdrawal or recombinant human TSH (rhTSH/Thyrogen)
- A low-iodine diet for 1-2 weeks prior to RAI therapy depletes the body's iodine pool, increasing the proportion of I-131 taken up by residual thyroid tissue
- Post-therapy whole body scan often reveals additional foci of disease not seen on pre-therapy diagnostic scans due to the higher therapeutic dose
- Stimulated thyroglobulin is a critical tumor marker for monitoring differentiated thyroid cancer; rising levels post-treatment suggest recurrent or persistent disease

---

## Case 2: Myocardial Perfusion Imaging for CAD

### Patient Presentation
**Demographics:** 59-year-old male construction foreman

**Chief Complaint:** "I get chest tightness when I walk uphill at work."

**History of Present Illness:**
A 59-year-old male construction foreman presents with a 3-month history of exertional chest tightness. The discomfort occurs when he walks uphill to construction sites or climbs stairs carrying equipment. It is described as a pressure-like sensation across his anterior chest, occasionally radiating to his left shoulder. The symptoms resolve within 3-5 minutes of rest. He has not experienced chest pain at rest, nocturnal symptoms, or dyspnea on exertion beyond what he attributes to the chest tightness. The symptoms have been gradually worsening; 3 months ago they occurred only with heavy lifting, but now occur with moderate uphill walking.

His primary care physician performed an initial assessment. His pre-test probability for coronary artery disease was estimated at 65% using the Duke Clinical Score (age, sex, symptoms). Given his intermediate pre-test probability and ability to exercise, he was referred for exercise myocardial perfusion imaging (MPI) with Tc-99m sestamibi SPECT.

**Past Medical History:**
- Hypertension (10 years)
- Type 2 diabetes mellitus (5 years)
- Hyperlipidemia
- Obesity (BMI 30.8)
- No prior cardiac history

**Medications:**
- Metoprolol succinate 50 mg daily (held 48 hours prior to stress test per protocol)
- Lisinopril 20 mg daily
- Metformin 1000 mg BID
- Atorvastatin 40 mg daily
- Aspirin 81 mg daily

**Social History:**
- Construction foreman, physically demanding work
- Former smoker (quit 2 years ago, 20 pack-year history)
- 1-2 beers on weekends
- Married, three children
- Diet: fast food 3-4 times per week

**Family History:**
- Father: MI at age 62, survived with stenting
- Brother: MI at age 55

### Physical Examination
- **Vital Signs:** BP 142/88 mmHg, HR 74 bpm (off beta-blocker), RR 14/min, Temp 36.8°C, SpO2 98% on room air, BMI 30.8
- **General:** Stocky, muscular male in no acute distress
- **Cardiovascular:** Regular rate and rhythm, no murmurs, S4 gallop at apex, no S3
- **Lungs:** Clear bilaterally
- **Abdomen:** Obese, soft, non-tender
- **Extremities:** No edema, pulses 2+ throughout

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| Fasting glucose | 148 mg/dL | 70-100 mg/dL |
| HbA1c | 7.8% | <7.0% |
| Total cholesterol | 228 mg/dL | <200 mg/dL |
| LDL | 132 mg/dL | <100 mg/dL |
| HDL | 36 mg/dL | >40 mg/dL |
| Triglycerides | 298 mg/dL | <150 mg/dL |
| Creatinine | 1.0 mg/dL | 0.7-1.3 mg/dL |
| Resting ECG | Normal sinus rhythm, no ST-T changes | - |

**Imaging/Additional Studies:**
- **Exercise Stress Test (Bruce Protocol):**
  - Exercise duration: 7 minutes 12 seconds (Stage 3)
  - Peak HR: 148 bpm (92% of age-predicted maximum -- adequate stress)
  - Peak BP: 198/94 mmHg
  - Symptoms: Reproduced typical chest tightness at 6 minutes, resolved in recovery
  - ECG: 2 mm horizontal ST-segment depression in leads V4-V6 at peak exercise, resolving in recovery
  - Duke Treadmill Score: -8 (moderate risk)
- **Tc-99m Sestamibi SPECT Myocardial Perfusion Imaging:**
  - **Stress images:** Moderate-sized, moderate-intensity reversible perfusion defect in the anterior wall and anteroseptum (LAD territory), involving approximately 15% of the left ventricular myocardium
  - **Rest images:** Normal perfusion throughout (complete reversibility confirms ischemia, not infarction)
  - **Gated SPECT:** LVEF 58%, normal wall motion at rest, anterior wall hypokinesis on post-stress gated images (ischemic stunning)
  - **Transient ischemic dilation (TID):** Present (stress/rest LV cavity ratio 1.18; abnormal >1.12) -- suggests extensive ischemia or multivessel disease
  - **Summed Stress Score (SSS):** 12 (moderate ischemia)
  - **Summed Difference Score (SDS):** 10 (moderate reversible ischemia)

### Clinical Image

![Myocardial Perfusion SPECT Interpretation](case_02_image.jpg)

*Diagram showing a bull's-eye (polar) map display of myocardial perfusion SPECT imaging comparing stress and rest images, with color scale indicating normal perfusion versus reversible ischemic defects in the LAD coronary artery territory. Source: Educational illustration.*

### Diagnosis
**Exercise-Induced Myocardial Ischemia in the LAD Territory (Moderate-Sized Reversible Perfusion Defect), Consistent with Hemodynamically Significant Coronary Artery Disease**

**Key Diagnostic Criteria:**
- Reproducible exertional angina during stress test
- 2 mm horizontal ST depression on stress ECG (V4-V6)
- Moderate-sized reversible perfusion defect in anterior wall and anteroseptum (LAD territory)
- Complete reversibility on rest images (no infarction)
- Transient ischemic dilation (TID) present, suggesting extensive ischemia
- Post-stress wall motion abnormality (ischemic stunning)
- SSS 12 and SDS 10 indicating moderate ischemic burden (>10% ischemic myocardium)

### Treatment Plan
1. **Cardiac catheterization:** Recommended given >10% ischemic myocardium on SPECT and high-risk features (TID, ischemic stunning); coronary angiography with FFR-guided PCI if appropriate
2. **Optimize medical therapy:**
   - Restart metoprolol succinate 50 mg, titrate to HR 55-60
   - Start long-acting nitrate (isosorbide mononitrate 30 mg daily) for angina
   - Increase atorvastatin to 80 mg daily (target LDL <70)
   - Add ezetimibe if LDL not at goal
3. **Diabetes optimization:** Add SGLT2 inhibitor (empagliflozin 10 mg) for cardiovascular benefit
4. **Lifestyle modification:** Cardiac rehabilitation referral, Mediterranean diet counseling, weight loss goal of 10%
5. **Activity modification:** Avoid heavy exertional activity until revascularization decision
6. **Follow-up MPI:** If treated medically, repeat in 1-2 years to assess ischemic burden

### Key Learning Points
- Myocardial perfusion imaging with Tc-99m sestamibi SPECT evaluates the physiological significance of coronary artery stenoses by detecting relative differences in myocardial blood flow between stress and rest
- A reversible perfusion defect indicates ischemia (viable myocardium with flow-limiting stenosis), while a fixed defect indicates scar/infarction
- Transient ischemic dilation (TID) is a high-risk finding on SPECT that suggests extensive ischemia, balanced multivessel ischemia, or subendocardial hypoperfusion
- The summed difference score (SDS) quantifies the extent of reversible ischemia; >10% ischemic myocardium is the threshold at which revascularization may provide survival benefit over medical therapy alone
- Exercise stress is preferred over pharmacologic stress when the patient can exercise adequately (achieving >85% age-predicted maximum heart rate) as it provides additional prognostic information from exercise capacity and hemodynamic response

---

## Case 3: PET/CT for Lymphoma Staging

### Patient Presentation
**Demographics:** 22-year-old male college student

**Chief Complaint:** "I've had a lump in my neck for about 6 weeks and I've been having drenching night sweats."

**History of Present Illness:**
A 22-year-old male college student presents after noticing a painless, progressively enlarging mass in his left neck 6 weeks ago. He initially attributed it to a swollen gland from a viral illness, but it has continued to grow. Over the past 3 weeks, he has developed drenching night sweats requiring him to change his sheets, unintentional weight loss of 5 kg (8% body weight), and intermittent fevers up to 38.5°C, predominantly in the evening. He also reports generalized pruritus without rash and an unusual symptom of sharp left neck pain after drinking alcohol (pathognomonic for Hodgkin lymphoma, though rare).

He was seen by his campus health center, which obtained a CT scan showing bulky mediastinal and left cervical lymphadenopathy. He was referred to hematology-oncology, and an excisional biopsy of the left cervical node was performed.

Pathology revealed classical Hodgkin lymphoma, nodular sclerosis subtype. He has been referred for F-18 FDG PET/CT for staging.

**Past Medical History:**
- No significant medical history
- No prior malignancy
- Up to date on immunizations including HPV

**Medications:**
- None
- Acetaminophen PRN for fevers

**Social History:**
- College junior, biology major
- Non-smoker
- Social alcohol (reported alcohol-induced lymph node pain)
- No illicit drug use
- Lives in dormitory

**Family History:**
- No family history of lymphoma or hematologic malignancy
- Maternal grandmother: breast cancer at age 70

### Physical Examination
- **Vital Signs:** BP 118/72 mmHg, HR 82 bpm, RR 14/min, Temp 37.8°C, SpO2 99% on room air, Weight 58 kg (baseline 63 kg 2 months ago)
- **General:** Thin young male, appears fatigued, no acute distress
- **Lymph nodes:**
  - Left anterior cervical chain: 4 cm firm, non-tender, rubbery, mobile mass
  - Left supraclavicular: 2 cm firm node
  - Right cervical: no palpable lymphadenopathy
  - Bilateral axillary: no palpable lymphadenopathy
  - Bilateral inguinal: small (<1 cm), soft, mobile nodes (likely reactive)
- **HEENT:** Oropharynx clear, no Waldeyer ring involvement
- **Cardiovascular:** Regular rate and rhythm, no murmurs
- **Lungs:** Clear bilaterally, no dullness to percussion
- **Abdomen:** Soft, non-tender, no hepatosplenomegaly, no palpable masses
- **Skin:** No rashes, excoriations from scratching on bilateral forearms

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| WBC | 11,800/µL | 4,500-11,000/µL |
| Hemoglobin | 11.2 g/dL | 13.5-17.5 g/dL |
| Platelets | 442,000/µL | 150,000-400,000/µL |
| ESR | 68 mm/hr | 0-15 mm/hr |
| LDH | 312 U/L | 140-280 U/L |
| Albumin | 3.2 g/dL | 3.5-5.0 g/dL |
| Alkaline phosphatase | 98 U/L | 44-147 U/L |
| Uric acid | 7.8 mg/dL | 3.5-7.2 mg/dL |
| Hepatitis B surface antigen | Negative | Negative |
| HIV | Negative | Negative |
| Beta-hCG | <1 mIU/mL | <5 mIU/mL |

**Pathology:**
- Excisional biopsy: Classical Hodgkin lymphoma, nodular sclerosis subtype
- Reed-Sternberg cells positive for CD30 and CD15
- Negative for CD20 (excludes nodular lymphocyte-predominant HL)
- EBV (EBER) in situ hybridization: Negative

**Imaging/Additional Studies:**
- **F-18 FDG PET/CT (Staging):**
  - **Left cervical chain:** Multiple intensely FDG-avid nodes, largest 4.2 x 3.1 cm, SUVmax 14.8
  - **Left supraclavicular:** FDG-avid node, 2.3 cm, SUVmax 11.2
  - **Mediastinum:** Bulky anterior mediastinal mass measuring 10.2 x 7.8 cm (mediastinal mass ratio 0.38 -- bulky disease), SUVmax 16.4, encasing but not compressing great vessels
  - **Bilateral hilar:** Mildly FDG-avid nodes, largest 1.8 cm, SUVmax 8.2
  - **Spleen:** Diffusely increased FDG uptake, SUVmax 5.4 (above normal liver background of 3.2), no focal lesions
  - **Subdiaphragmatic:** No FDG-avid lymphadenopathy
  - **Bone marrow:** No focal FDG-avid osseous lesions
  - **Liver, lungs, other organs:** No evidence of extranodal disease
  - **Deauville Score (baseline):** 5 (intense uptake above liver, as expected for staging)

### Clinical Image

![PET/CT Lymphoma Staging](case_03_image.jpg)

*Diagram showing maximum intensity projection (MIP) image from F-18 FDG PET/CT in a patient with Hodgkin lymphoma, demonstrating FDG-avid cervical, supraclavicular, mediastinal, and hilar lymphadenopathy with the Deauville five-point scale for response assessment. Source: Educational illustration.*

### Diagnosis
**Classical Hodgkin Lymphoma, Nodular Sclerosis Subtype, Stage IIBS (B Symptoms: Fevers, Night Sweats, Weight Loss >10%; S: Splenic Involvement; Bulky Mediastinal Disease)**

**Key Diagnostic Criteria:**
- Reed-Sternberg cells on biopsy (CD30+, CD15+)
- PET/CT demonstrating FDG-avid disease above and below the diaphragm (cervical, supraclavicular, mediastinal, hilar = above; splenic involvement = below) -- Stage III
- B symptoms present: fevers >38°C, drenching night sweats, weight loss >10% in 6 months
- Bulky mediastinal disease (>10 cm or mediastinal mass ratio >0.33)
- Diffuse splenic FDG uptake above liver background indicating involvement
- International Prognostic Score (IPS): 3 points (albumin <4, hemoglobin <10.5 -- borderline, WBC >15,000 -- no; stage IV -- no; age >45 -- no; male -- yes; lymphocyte count -- adequate)

### Treatment Plan
1. **Chemotherapy:** ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 cycles, with consideration of escalation to BEACOPP if interim PET shows inadequate response
2. **Interim PET/CT:** After 2 cycles of ABVD (PET-2) to assess early metabolic response using Deauville criteria; Deauville 1-3 = adequate response (continue ABVD, may omit bleomycin); Deauville 4-5 = inadequate response (escalate to BEACOPP or alternative)
3. **End-of-treatment PET/CT:** After completion of chemotherapy to confirm complete metabolic response (Deauville 1-3)
4. **Consolidative radiation:** Involved-site radiation therapy (ISRT) 30 Gy to bulky mediastinal disease if complete metabolic response achieved; consider omission if PET-2 negative (per RAPID/RATHL trial data)
5. **Fertility preservation:** Urgent sperm banking before chemotherapy initiation (ABVD has lower gonadotoxicity than BEACOPP but counseling still recommended)
6. **Pre-treatment:** Echocardiogram (baseline for doxorubicin), PFTs (baseline for bleomycin), hepatitis B/C screening, HIV testing, port placement
7. **Supportive care:** Antiemetics, growth factor support if needed, Pneumocystis prophylaxis if BEACOPP escalation, psychosocial support and academic accommodations

### Key Learning Points
- F-18 FDG PET/CT is the standard of care for initial staging and response assessment in Hodgkin lymphoma, replacing CT-only staging which misses metabolically active disease in normal-sized nodes and splenic involvement
- The Deauville five-point scale (1=no uptake, 2=uptake ≤ mediastinum, 3=uptake > mediastinum but ≤ liver, 4=uptake moderately > liver, 5=uptake markedly > liver or new lesions) provides a standardized framework for response assessment
- Interim PET/CT after 2 cycles (PET-2) is a powerful prognostic tool: a negative PET-2 predicts >90% progression-free survival and may allow treatment de-escalation (bleomycin omission or fewer cycles)
- PET/CT has largely replaced bone marrow biopsy for staging in Hodgkin lymphoma, as it has high sensitivity for marrow involvement (focal FDG-avid osseous lesions)
- Bulky mediastinal disease is an important prognostic factor in Hodgkin lymphoma and may influence decisions regarding consolidative radiation therapy